Bang, Seunghwan Park, Byeongmin Park, Jae Chul JIN, HA RIN Shim, Ji Sung Koo, Jahyun LEE, KWAN HYI Shim, Man Kyu Kim, Hojun 2025-03-21T08:00:24Z 2025-03-21T08:00:24Z 2025-03-19 2025-03 1936-0851 https://pubs.kist.re.kr/handle/201004/151954 The extracellular matrix (ECM) is a complex network of biomolecules with varying pore sizes, posing a challenge for the effective penetration of lipid nanoparticles. In contrast, cell-derived lipid nanoparticles, such as exosomes, have demonstrated the ability to travel to distant organs, indicating their capacity to penetrate the ECM. Here, we designed exosome-like vesicles (ELVs) inspired by exosomes' distinct transport phenomena. Specifically, we integrated three exosomal components (anionic lipid, cholesterol, and aquaporin-1) associated with transport into our ELVs to mimic the superior diffusion behavior of exosomes over synthetic lipid nanoparticles. Surprisingly, both bulk- and single-particle-diffusion studies revealed a more than 33 times increase in the effective diffusion coefficient within model ECM compared to conventional lipid nanoparticles. Furthermore, ELVs show an 80% increase in the effective diffusion coefficient within biological tissues. The excellent transport behavior of ELVs was further validated in vivo, where intratumoral injection showcased their superior transport. These findings provide insights into lipid nanoparticle design for improved tissue penetration. English American Chemical Society Exosome-Inspired Lipid Nanoparticles for Enhanced Tissue Penetration Article 10.1021/acsnano.4c16629 1 ACS Nano, v.19, no.9, pp.8882 - 8894 ACS Nano 19 9 8882 8894 N scie scopus 001435203500001 2-s2.0-86000141624 Chemistry, Multidisciplinary Chemistry, Physical Nanoscience & Nanotechnology Materials Science, Multidisciplinary Chemistry Science & Technology - Other Topics Materials Science Article COLLAGEN EXTRACELLULAR-MATRIX STRATEGIES DRUG-DELIVERY tissue penetration small-angle X-rayscattering exosome lipid nanoparticle single-particle tracking